Alexis Sanchez will be out for up to eight weeks after sustaining knee ligament damage.
The Chile forward broke down in Man Utd’s 3-2 win against Southampton on Saturday.
United’s doctors immediately feared ligament damage - and tests on Sunday confirmed that prognosis.
Sanchez suffered a distension of the medial ligament in his right knee, which will see him miss the majority of the rest of the season.
Chile national team doctor Pedro Onate told El Mercurio the 30-year-old would be “between six and eight weeks without playing.”
Sanchez has only recently returned from a six-week absence after sustaining ligament damage in training in November.
He has struggled to hold down a place in Ole Gunnar Solskjaer’s side and his latest setback will place fresh doubts over his long-term future.
United face Paris Saint-Germain in the Champions League on Wednesday with Solskjaer facing an injury crisis.
Ander Herrera, Jesse Lingard, Nemanja Matic, Anthony Martial, Juan Mata, Phil Jones and Antonio Valencia are also out.
United will also be without the suspended Paul Pogba.
